Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China; Department of Cardiology, The Third Hospital of Mianyang/Sichuan Mental Health Center, Mianyang 621000, Sichuan, China.
Department of Cardiology, The Third Hospital of Mianyang/Sichuan Mental Health Center, Mianyang 621000, Sichuan, China.
Neurosci Lett. 2022 Sep 25;788:136860. doi: 10.1016/j.neulet.2022.136860. Epub 2022 Aug 27.
There are negative correlations between indices of heart rate variability (HRV) and markers of inflammation. The inflammation plays an important role in myocardial damages after myocardial infarction (MI). Our previous study found that fastigial nucleus electrostimulation (FNS) improved abnormal HRV in a rat model of MI. Whether it can reduce inflammation and improve cardiac function after MI and the underlying mechanisms remain unknown. 66 Sprague Dawley rats were randomly divided into 4 groups as follows: i) Sham group (sham operation); ii) MI group (left anterior descending coronary artery ligation); iii) FNS + MI group (left fastigial nucleus electrostimulation plus MI); iv) FNL + FNS + MI group (left fastigial nucleus lesion plus FNS plus MI). The serum expressions of acetylcholine (ACh), pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and anti-inflammatory cytokines IL-10 were measured by ELISA. Subsequently, the infarct size, the infiltration of inflammatory cells, the fibrotic area, and cardiac function were also evaluated. Additionally, the expressions of the cholinergic anti-inflammatory pathway (CAP)-related proteins in infarct tissue, such as nuclear factor kappa B (NF-κB) and singal transducers and activators of transcription 3 (STAT3), were determined by Western blot. We found that FNS significantly increased ACh and IL-10 levels in serum, and decreased TNF-α and IL-6 levels. FNS significantly attenuated inflammatory cell infiltration, reduced infarct size, decreased fibrosis, increased left ventricular ejection fraction, and reduced mortality. Besides, the ratios of phosphorylated-STAT3/STAT3 and phosphorylated-NF-κB/NF-κB in infarct tissue significantly elevated after MI. FNS reduced the ratios of p-STAT3/STAT3 and p-NF-κB/NF-κB in infarct tissue. The protective effects of FNS were partially reversed by the fastigial nucleus lesion. Our data suggested that FNS can alleviate the inflammation after MI, and its cardiac neuroprotective mechanism may be achieved by increasing vagal tone, releasing ACh, and further activating the CAP via α7 nicotinic acetylcholine receptor. The precise mechanism remains to be elucidated.
心率变异性（HRV）指数与炎症标志物呈负相关。炎症在心肌梗死后心肌损伤中起重要作用。我们之前的研究发现，电刺激小脑顶核（FNS）可改善心肌梗死后大鼠模型的异常 HRV。但电刺激小脑顶核是否能减轻心肌梗死后的炎症并改善心功能，以及其潜在机制尚不清楚。66 只 Sprague Dawley 大鼠随机分为 4 组：i）假手术组（假手术）；ii）心肌梗死组（左前降支结扎）；iii）FNS+MI 组（左顶核电刺激+MI）；iv）FNL+FNS+MI 组（左顶核病变+FNS+MI）。通过 ELISA 法检测血清乙酰胆碱（ACh）、促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）以及抗炎细胞因子白细胞介素-10（IL-10）的表达。随后，还评估了梗死面积、炎症细胞浸润、纤维化面积和心功能。此外，还通过 Western blot 法测定梗死组织中胆碱能抗炎通路（CAP）相关蛋白，如核因子-κB（NF-κB）和信号转导子和转录激活子 3（STAT3）的表达。结果发现，FNS 显著增加了血清中 ACh 和 IL-10 的水平，降低了 TNF-α和 IL-6 的水平。FNS 显著减轻了炎症细胞浸润，减少了梗死面积，减少了纤维化，增加了左心室射血分数，降低了死亡率。此外，心肌梗死后梗死组织中磷酸化-STAT3/STAT3 和磷酸化-NF-κB/NF-κB 的比值显著升高。FNS 降低了梗死组织中 p-STAT3/STAT3 和 p-NF-κB/NF-κB 的比值。小脑顶核病变部分逆转了 FNS 的保护作用。我们的数据表明，FNS 可减轻心肌梗死后的炎症，其心脏神经保护机制可能是通过增加迷走神经张力、释放 ACh，并进一步通过α7 型烟碱型乙酰胆碱受体激活 CAP 来实现。其确切机制仍有待阐明。
